DISSERTATION RESEARCH: Population genetics and the evolution of innate immunity in house mice

在家鼠（家鼠）中，免疫相关蛋白结构域占基因组中进化最快的蛋白结构域类别的75%，这一模式已在多种动物和植物中得到证实。如此快速的进化与自然选择是一致的，但并没有告诉我们选择是如何在种群内产生这种种间模式的。该项目将探索(i)最能解释快速免疫基因进化的选择模式和（ii）特定病原体如何影响这些基因。具体而言，将确定野生家鼠种群中10个先天免疫基因和10个非免疫控制基因的DNA序列。将对选定病原体的流行率进行量化，并将这些感染表型与抗性等位基因进行比较，以检验统计相关性。很少有研究关注先天免疫的进化，先天免疫是哺乳动物对感染的第一个也是最快的反应。特别是，目前尚不清楚免疫基因的快速进化是由于对新变体的反复选择还是选择维持多种变体。这项工作将提高我们对免疫系统进化的理解，这是人类健康的一个重要模型，并为无脊椎动物和植物的免疫研究提供有用的对比。这项工作还将有助于培养一名美洲原住民女博士生。

In house mice (Mus domesticus), immunity-related protein domains comprise 75% of the most rapidly evolving protein domain classes in the genome, a pattern that has been documented in diverse animals and plants. Such rapid evolution is consistent with natural selection, but does not tell us how selection acted within populations to produce this between-species pattern. This project will explore both (i) the mode of selection which best explains rapid immunity gene evolution and (ii) how specific pathogens affect these genes. Specifically, DNA sequences will be determined for ten innate immunity genes and ten non-immunity control genes in a population of wild house mice. Prevalence of selected pathogens will be quantified, and these infection phenotypes will be compared with resistance alleles to test for a statistical association.Few studies have focused on the evolution of innate immunity, the first and fastest response to infections, in mammals. In particular, it remains unclear whether rapid evolution of immunity genes is due to recurrent selection for novel variants or selection to maintain multiple variants. This work will improve our understanding of immune system evolution in an important model of human health, and provide a useful contrast to studies of immunity in invertebrates and plants. This work will also help train a female Native American Ph.D. student.